‘Building a perfect body’: control of vertebrate organogenesis by PBX-dependent regulatory networks

Selleri, Licia; Zappavigna, Vincenzo; Ferretti, Elisabetta

doi:10.1101/gad.318774.118

Cited by 44 publications

(54 citation statements)

References 185 publications

(275 reference statements)

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“…Because of the redundancy of, and early requirements for, Pbx proteins in mouse embryogenesis (reviewed in Selleri et al 2019), we needed to make use of conditional loss-offunction in Myf5 Cre/+ ;Pbx1 fl/fl ;Pbx2 -/compound mutants. A similar approach, using different conditional Cre lines, has previously been taken to study Pbx functions in craniofacial, spleen, and spinal cord motor neuron development and in adult neurogenesis (Ferretti et al, 2011;Grebbin et al, 2016;Hanley et al, 2016;Koss et al, 2012;Losa et al, 2018;Welsh et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…In mouse, previous studies have shown that Pbx1 is expressed broadly in embryonic somites and is required for multiple developmental programs Selleri et al, 2001;Selleri et al, 2019). To investigate the requirements for Pbx factors in mouse muscle differentiation, we examined mouse embryos lacking Pbx1 (Pbx1 -/-; Selleri et al, 2001).…”

Section: Loss Of Pbx1 Has Little Effect On Early Mouse Muscle Differementioning

confidence: 99%

“…Studies in zebrafish and mouse embryos, as well as in mammalian cell culture models, have shown that Pbx proteins bind with Myod1 on the promoters of a subset of Myod1 target genes, including Myog and mylpfa (Berkes et al, 2004;Cho et al, 2015;de la Serna et al, 2005;Dell'Orso et al, 2016;Heidt et al, 2007;Maves et al, 2007;Pliner et al, 2018). Pbx proteins can bind silent Myod1 target gene promoters prior to Myod1 binding and muscle differentiation, suggesting the potential for Pbx proteins to function as pioneer factors in skeletal muscle differentiation (Berkes et al, 2004;Cho et al, 2015;de la Serna et al, 2005;Dell'Orso et al, 2016; for discussion of Pbx proteins as pioneer factors, see Schulte, 2017 andSelleri et al, 2019). Pbx genes are broadly expressed during embryogenesis and are required for many aspects of mouse embryo development (reviewed in Moens and Selleri, 2006;and Selleri et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Pbx proteins can bind silent Myod1 target gene promoters prior to Myod1 binding and muscle differentiation, suggesting the potential for Pbx proteins to function as pioneer factors in skeletal muscle differentiation (Berkes et al, 2004;Cho et al, 2015;de la Serna et al, 2005;Dell'Orso et al, 2016; for discussion of Pbx proteins as pioneer factors, see Schulte, 2017 andSelleri et al, 2019). Pbx genes are broadly expressed during embryogenesis and are required for many aspects of mouse embryo development (reviewed in Moens and Selleri, 2006;and Selleri et al, 2019). However, these previous studies have not directly addressed the requirements for Pbx proteins in mammalian skeletal muscle development.…”

Section: Introductionmentioning

confidence: 99%

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Evolutionarily conserved regulation of embryonic fast-twitch skeletal muscle differentiation by Pbx factors

Farr¹,

Risolino

et al. 2020

Preprint

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Vertebrate skeletal muscles are composed of both slow-twitch and fast-twitch fiber types. How the differentiation of distinct fiber types is activated during embryogenesis is not well characterized. Skeletal muscle differentiation is initiated by the activity of the myogenic basic helix-loop-helix (bHLH) transcription factors Myf5, Myod1, Myf6, and Myog. Myod1 functions as a muscle master regulatory factor and directly activates muscle differentiation genes, including those specific to both slow and fast muscle fibers. Our previous studies showed that Pbx TALE-class homeodomain proteins bind with Myod1 on the promoter of the zebrafish fast muscle gene mylpfa and are required for proper activation of mylpfa expression and the fasttwitch muscle-specific differentiation program in zebrafish embryos. Pbx proteins have also been shown to bind regulatory regions of muscle differentiation genes in mammalian muscle cells in culture. Here, we use new zebrafish mutant strains to confirm the essential roles of zebrafish Pbx factors in embryonic fast muscle differentiation. Furthermore, we examine the requirements for Pbx genes in mouse embryonic skeletal muscle differentiation, an area that has not been investigated in the mammalian embryo. Removing Pbx1 function from skeletal muscle in Myf5 Cre/+; Pbx1 fl/fl mouse embryos has minor effects on embryonic muscle development.However, concomitantly deleting Pbx2 function in Myf5 Cre/+ ;Pbx1 fl/fl ;Pbx2 -/mouse embryos causes delayed activation and reduced expression of fast muscle differentiation genes. In the mouse, Pbx1/Pbx2-dependent fast muscle genes closely match those that have been previously shown to be dependent on murine Six1 and Six4. This work establishes evolutionarily conserved requirements for Pbx factors in embryonic fast muscle differentiation. Our studies are revealing how Pbx homeodomain proteins help direct specific cellular differentiation pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Loss Of Pbx1 Has Little Effect On Early Mouse Muscle Differementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evolutionarily conserved regulation of embryonic fast-twitch skeletal muscle differentiation by Pbx factors

Farr¹,

Risolino

et al. 2020

Preprint

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“…HOX association with three amino acid loop extension (TALE) HD TFs PBX, and PBX partner MEIS, is a widely accepted mechanism underlying HOX target specificity (Bobola and Merabet, 2017; Merabet and Mann, 2016; Selleri et al, 2019). HOX-TALE cooperativity increases the affinity and sequence selectivity of HOX TFs in vitro (Merabet and Mann, 2016).…”

Section: Introductionmentioning

confidence: 99%

HOX paralogs selectively convert binding of ubiquitous transcription factors into tissue-specific patterns of enhancer activation

Bridoux

Zarrineh

Mallen

et al. 2019

Preprint

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19Gene expression programs determine cell fate in embryonic development and their 20 dysregulation results in disease. Transcription factors (TFs) control gene expression by 21 binding to enhancers, but how TFs select and activate their target enhancers is still unclear. 22HOX TFs share conserved homeodomains with highly similar sequence recognition 23properties, yet they impart the identity of different animal body parts. To understand how 24 HOX TFs control their specific transcriptional programs in vivo, we compared HOXA2 and 25 HOXA3 binding profiles in the mouse embryo. HOXA2 and HOXA3 directly cooperate with 26 TALE TFs and selectively target different subsets of a broad TALE chromatin platform. 27Binding of HOX and tissue-specific TFs convert low affinity TALE binding into high 28 confidence, tissue-specific binding events, which bear the mark of active enhancers. We 29 propose that HOX paralogs, alone and in combination with tissue-specific TFs, generate 30 tissue-specific transcriptional outputs by modulating the activity of TALE TFs at selected 31 enhancers. 32 33 Introduction 34 Gene expression programs instruct and maintain cell fate in embryonic development and 35 adult tissue homeostasis. Transcription factors (TFs) control gene expression by binding to 36 enhancers (Reiter et al., 2017; Spitz and Furlong, 2012). However, we still have no clear 37 idea of how TFs select their precise sets of target enhancers. While TFs contain DNA 38 binding domains which recognize DNA in a sequence-specific manner, these interactions 39 are typically insufficient to direct a TF to its functional targets. 40Transcriptional regulation is mediated by TFs working together, rather than in isolation. The 41 widespread occurrence of collaborative TF binding is imposed by chromatin. A single TF 42 cannot easily compete with nucleosomes to access DNA, but multiple TFs that recognize 43 closely spaced binding sites can effectively displace nucleosomes and indirectly facilitate 44 each other's binding (Mirny, 2010; Moyle-Heyrman et al., 2011). Such indirect cooperativity 45 can also result in TFs recognizing low affinity sites, i.e. sites that deviate from their optimal 46 3 consensus in vitro (Farley et al., 2015). Recent observations indicate that TF cooperativity 47 does not end at binding enhancers: clusters of enhancer-bound TFs concentrate co-48 activators and other nuclear factors via dynamic fuzzy interactions, driven by their 49 intrinsically disordered regions (IDRs). IDRs function in molecular recognition and mediate 50 the interaction with a diversity of regulatory proteins (Cumberworth et al., 2013; Staby et al., 51 2017) to promote the liquid-liquid phase transition associated with gene activation (Boija et 52 al., 2018). Thus, the formation, on DNA segments, of regulatory complexes made of different 53 combinations of factors, is key to activation of gene expression. These distinct combinations 54 of TFs produce virtually inexhaustible flavours of gene expression and cell fate (Spitz and 55 Furlong, 2012).56...

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A novel pathogenic variant c.262delA in PBX1 causing oligomeganephronia identified using whole‐exome sequencing and a literature review

Hu,

Yang,

Wang

et al. 2023

American J of Med Genetics Pt A

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Oligomeganephronia (OMN) is a rare congenital renal hypoplasia reported more often in children than in adults. The diagnosis of OMN relies on renal biopsy and exhibits a significant reduction in the number of glomeruli and pronounced glomerular hypertrophy. Here, we report the case of an 8‐year‐old boy with recurrent proteinuria and abnormal external ears. A renal biopsy revealed large and rare glomeruli. The histological findings confirmed the diagnosis of OMN. Whole‐exome sequencing of the patient revealed a new pathogenic variant in PBX1 (hg19, NM_002585, c.262delA, p.Thr88Glnfs*3). The PBX1 gene encodes a transcription factor whose pathogenic variants can result in congenital renal and urinary system anomalies, with or without hearing loss, abnormal ears, and developmental retardation (CAKUTED). This is the first report to detect PBX1 pathogenic variants in children with OMN, a novel phenotype of human PBX1 pathogenic variants. We performed functional prediction analyses of deletions in the corresponding structural domains. We summarized 27 cases of PBX1 single pathogenic variants reported between 2003 and 2023 in terms of truncating and missense pathogenic variants, which can deepen our understanding of the PBX1 structural domain and expand our knowledge of the PBX1 genotype and phenotype.

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‘Building a perfect body’: control of vertebrate organogenesis by PBX-dependent regulatory networks

Cited by 44 publications

References 185 publications

Evolutionarily conserved regulation of embryonic fast-twitch skeletal muscle differentiation by Pbx factors

Evolutionarily conserved regulation of embryonic fast-twitch skeletal muscle differentiation by Pbx factors

HOX paralogs selectively convert binding of ubiquitous transcription factors into tissue-specific patterns of enhancer activation

A novel pathogenic variant c.262delA in PBX1 causing oligomeganephronia identified using whole‐exome sequencing and a literature review

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